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Updated: May 8, 2025

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Delayed but successful development of immune memory against SARS-COV-2 after B cell-depleting monotherapy

Nicolas Graf1,2, Joseph Bayerl3, Barbara Schmidt4

  • 1Medical Department II, Section Oncology, Donau-Isar-Klinikum Deggendorf, Deggendorf, Germany. nicolasgraf@gmx.de.

Infection
|May 7, 2025
PubMed
Abstract

Insights

Patients on CD20-directed therapies show improved antibody responses to a third SARS-COV-2 vaccine when therapy is monotherapy and at least 6 months post-treatment. Delayed immune responses are also possible in these patients.

Area of Science:

  • Immunology
  • Vaccinology
  • Oncology

Background:

  • Patients receiving CD20-directed therapies often have insufficient neutralizing antibody titers against SARS-COV-2 after two vaccinations.
  • This study investigates the impact of additional vaccinations in this patient population.

Purpose of the Study:

  • To evaluate the efficacy of a third and fourth mRNA-based SARS-COV-2 vaccination in patients on CD20-directed therapies.
  • To identify predictive factors for adequate humoral immune response.

Main Methods:

  • A prospective, observational study included patients receiving monoclonal CD20 antibodies (mCD20Ab).
  • SARS-COV-2 IgG titers were measured before and after the third vaccination.
  • Patients without adequate response proceeded to a fourth vaccination. Tolerability and influencing factors were analyzed.

Main Results:

  • Third vaccination was well-tolerated, showing a significant increase in IgG titers but not clinically relevant seroconversion rates.
  • Patients over 65 years and those treated with mCD20Ab more than 6 months prior benefited.
  • Monotherapy with mCD20Ab correlated with immediate or delayed responses, while combination therapy patients were non-responders.

Conclusions:

  • An interval of at least 6 months after the last mCD20Ab administration and mCD20Ab monotherapy are favorable for humoral response to a third SARS-COV-2 vaccine.
  • Delayed immune responses are possible, warranting investigation at later time points.
Keywords:
AntibodiesB-cell depletionImmune memorySARS-CoV-2Vaccination

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